N-[2,4-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]phenyl]methanesulfonamide is an important herbicide in the agrochemical industry. The ability for general, efficient syntheses of sulfonamides under mild conditions is still of continuing interest to the industry. Recently many efforts have been made for the development of novel processes to make sulfonamides such as described in (a) S. W. Wright and K. N. Hallstrorn, J. Org. Chem., 2006, 71, 1080-1084; (b) A. R. Katritzky, A. A. A. Abdel-Fattah, A. V. Vakulenko and H. Tao, J. Org. Chem., 2005, 70, 9191-9197; (c) S. Caddick, J. D. Wilden and D. B. Judd, J. Am. Chem. Soc., 2004, 126, 1024-1025; (d) R. Pandya, T. Murashima. L. Tedesehi and A. G. M. Barrett, J. Org. Chem 2003, 68, 8274-2876; (e) J. W. Lee, Y. Q. Louie, D. P. Walsh and Y.-T. Chang, J. Comb. Chem., 2003, 5, 330-335; (f) C. G. Frost, J. P. Hartley and D. Griffin, Synlett, 2002, 11, 1928-1930.
However, the conventional synthesis for reaction of an amino compound and a sulfonyl chlorides is still the best method because of the simplicity of the reaction. Two general schemes for this reaction are widely used and described in the prior art. The first is to perform the reaction in organic solvents and employ organic amine bases to scavenge the acid that is generated for example as described in U.S. Pat. No. 4,818,275. Elevated temperature is often required, especially for the less reactive aniline substrates and bis-sulfonylation is a common side reaction, which makes isolation difficult and expensive and adds the further recycle of the stoichiometric quantity of acid scavenger used such as pyridine or triethyl amine as an unnecessary processing step. Modifications of this basic method can also be seen in the prior art for example with the use of catalytic quantity of acid scavengers and higher temperature boiling solvents such as described in U.S. Pat. No. 7,169,952.
The second general scheme uses modified Schotten-Baumann conditions. Here a typical procedure involves adding the sulfonyl chloride slowly into an amine solution in a biphasic system of organic solvents and basic (sodium carbonate or sodium hydroxide) aqueous solution such as described in (a) M. D. Surman, M. J. Mulvihill and M. J. Miller, Org. Lett., 2002, 4, 139-141; (b) W. Hu, Z. Guo, F. Chu, A. Bai, X. Yi, G. Cheng and J. Li, Bioorg. Med. Chem., 2003, 11, 1153-1160; (c) M. Medebielle, O. Onomura, R. Keirouz, E. Okada, H. Yano and T. Terauchi, Synthesis, 2002, 17, 2601-2608; (d) C. Goldenberg, R. Wandestrick and J. Richard, Eur. J. Med. Chem, 1977, 12, 81-86. Water as a reaction solvent is preferred over organic solvents due to cost, safety and environmental concerns.
Under these conditions, hydrolysis of the sulfonyl chlorides is the major competing reaction, which necessitates the use of excess sulfonyl chloride and results in diminishing yields. In both processes, the isolation and purification of the sulfonamide products are not straightforward due to the formation of bis-sulfonated impurities and large quantities of hydrolysed sulfonic acid by-products formed.
Accordingly, there exists a need to prepare N-(substituted aryl)sulfonamides directly from arylamines in an environmentally benign manner without the addition of an acid scavenger and without substantial formation of the bis(methanesulfonylamino) and hydrolyzed sulfonyl chloride by-products.